Have Researchers Found A Way To Turn Off Food Cravings?

Canada is dealing with an obesity challenge. At the moment, one in four adults and one in ten children are defined as being obese. One might believe the answer to obesity is simply to eat less and exercise more. Yet, over the last few decades, researchers have learned this condition is far more complex than initially believed.

LAGUNA DESIGN via Getty ImagesLeptin, molecular model. This hormone is produced by adipose (fat) tissue. It interacts with receptors in the brain's hypothalamus to signal when a person is full. It also circulates in the blood at levels proportionate to body fat, which allows the brain to regulate appetite and metabolism.

Canada is dealing with an obesity challenge. At the moment, one in four adults and one in ten children are defined as being obese. One might believe the answer to obesity is simply to eat less and exercise more. Yet, over the last few decades, researchers have learned this condition is far more complex than initially believed.

One of the troubles with obesity deals with consistent food cravings. One of the responsible molecules is known as POMC (meaning proopiomelanocortin). It's produced in the neurons of the hypothalamus and sends signals to the brain to reduce the hunger sensation. High levels lead to less appetite while low or no levels mean insatiable hunger.

The production of POMC is itself dependent on another hormone in the body, leptin. When leptin enters the hypothalamus, it signals the neurons to produce POMC and reduce appetite. If leptin levels decrease or are absent, the urge to eat may be unstoppable leading to weight gain.

In people with normal weight, this process works perfectly well. Yet, in obese individuals, the leptin response is altered somehow. The body seems to ignore leptin making it seem as if it is simply not there. This is known as leptin resistance.

Understanding leptin resistance has been an integral part of the study into appetite and weight gain. The best studied cause happens to be inflammation. When the body is in an inflamed state, leptin is ignored by the neurons in the hypothalamus. When this happens, the body learns to ignore the effects of leptin, creating a condition known as resistance. As this worsens, not only does a person gain weight, but also becomes vulnerable to other problems such as Type 2 Diabetes.

While inflammation may offer some perspective on leptin resistance, there was still no mechanism to understand why it occurs in the hypothalamus. That now has changed as last week, an international group of researchers revealed a mechanism inside the cells that may be the controlling factor in whether leptin can do its job effectively. The results suggest there may be an ON/OFF switch in the neuron controlling whether we feel satiated or hungry.

The team honed in on the process by which leptin actually signals POMC to form. They examined cells and tried to find one or more molecules capable of facilitating the message. They eventually found one particular protein, an enzyme called histone deacetylase five, or HDAC5. It seemed like the perfect choice as it is known as an ON/OFF regulator in the cell.

To mimic the OFF switch, they used mice missing the HDAC5 gene. To get the ON response, the team used mice with an overabundance of the protein. As expected, they saw a huge weight gain in the mice missing the gene while mice with unending amounts stayed lean. Once they had the models, the real experiments could happen to find the mechanism.

Using a variety of diets, the examined what was happening inside the mice at the cellular and molecular levels. With each different diet, the picture became clear and eventually a mechanism was deduced. But rather than a new discovery, the data revealed that when it comes to leptin resistance, HDAC5 controlled whether the cell would be receptive or resistant.

When leptin enters the hypothalamus, it tries to signal neurons to produce POMC. However, in order for this to happen, HDAC5 needs to be ON. If it is, the process to form POMC begins and soon after, the brain is told the person is no longer hungry. Yet, if HDAC5 is missing or in low supply - essentially OFF - then leptin simply cannot send the signal to make POMC. The hunger process begins to rise and soon, weight gain and obesity can occur.

Although this information is now known, there is still a missing piece to the obesity puzzle: how to control HDAC5 so it keeps the cell receptive to leptin. There may be, however, a natural way to do this. Back in 2011, a duo of researchers found that exercise may help to regulate HDAC5 in cells. Although the effects were not linked directly to leptin, this may offer a good reason to hit the gym or go for a run to help keep those hunger cravings at bay.